Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Finasteride, a 5 alpha-reductase inhibitor, was administered to normal male volunteers in a blinded placebo-controlled study at daily oral doses of 25, 50, and 100 mg for 11 days (part 1) and daily oral doses of 0.04, 0.12, 0.2, and 1.0 mg for 14 days (part 2). Results from part 1 showed a significant reduction in dihydrotestosterone (DHT) at all doses and a significant increase in both testosterone (T) and delta 4-androstenedione at the 50- and 100-mg doses. No change was seen in LH, FSH, cortisol, or estradiol levels. Serum lipids, including total cholesterol, low density lipoprotein, high density lipoprotein, and triglycerides were not affected by treatment. Results from part 2 again showed significant reduction in DHT at all doses. DHT levels returned to pretreatment values within 14 days of discontinuing treatment. Significant increases in T were observed only in the 1.0 mg group and only during the first 8 days of treatment. The T/DHT ratio increased with all doses and returned to baseline when drug was discontinued. The DHT metabolites and androstanediol glucuronide and androsterone glucuronide were significantly reduced at all doses. There were no significant adverse experiences reported during part 1 or 2. In conclusion, finasteride is well tolerated by normal volunteers and results in significant suppression of serum DHT at all doses tested.
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PMID:Effects of finasteride (MK-906), a 5 alpha-reductase inhibitor, on circulating androgens in male volunteers. 215 87

The deficiency of ovarian 17-ketosteroid reductase (17-KSR) was recently discovered to be a possible cause of polycystic ovarian disease (PCOD) in hirsute women. Forty three patients with PCOD (age range, 18-38 yr) were reevaluated to search for a hormonal pattern that might suggest an ovarian 17-KSR deficiency. Androstenedione, testosterone, FSH, LH, 17-hydroxyprogesterone, and dehydroepiandrosterone sulfate were evaluated basally on the day 17 of the menstrual cycle, when present, and after dynamic tests (ACTH stimulation, 1 mg im for 2 consecutive days; dexamethasone inhibition, 0.5 mg four times a day for 14 days; and cyproterone acetate treatment, 50 mg each day for 14 days) in three successive menstrual cycles or at 30-day intervals. All patients studied presented with hyperestronemia, abnormal gonadotropin pattern, and hyperandrogenism, but showed different responses of androstenedione and testosterone to dynamic tests. In two patients the hormonal pattern suggested an ovarian 17-KSR deficiency: in fact they showed plasma values of androstenedione (22 and 31.3 nmol/L, respectively) and estrone (628 and 849 pmol/L, respectively) that were greatly increased compared with other patients and with controls. Androstenedione did not increase after ACTH stimulation (21.5 and 32.1 nmol/L, respectively) and did not decrease after dexamethasone inhibition (21 and 29 nmol/L, respectively), but only decreased after cyproterone acetate treatment (8 and 10.8 nmol/L, respectively). An hCG test, performed during dexamethasone suppression, confirmed the diagnosis of ovarian 17-KSR defect in one of these two patients (patient 1). Two of three brothers of patient 1 (aged 25 and 34 yr) presented with persistent important pubertal gynecomastia; one brother also had severe oligospermia. These clinical findings and the high values of androstenedione/testosterone (0.85) and estrone/estradiol (4.1) ratios of baseline plasma levels compared with controls (0.18 and 2.1, respectively) suggested a partial testicular 17-KSR deficiency. Five other patients showed PCOD secondary to nonclassic 21-hydroxylase defect diagnosed on the basis of high 17-hydroxyprogesterone plasma values and highly responsive to ACTH. The remaining 36 patients showed increased values of androstenedione and testosterone after ACTH stimulation and a decrease of these two parameters after both dexamethasone inhibition and cyproterone acetate treatment. The discovery of the 17-KSR deficiency in men and women in the same family demonstrates genetic control of this enzyme similar in both sexes, confirming the hypothesis that this disorder is inherited as an autosomal recessive character. Finally, it is strongly supported that ovarian 17-KSR defect may cause a syndrome closely resembling PCOD.
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PMID:Ovarian 17-ketosteroid reductase deficiency as a possible cause of polycystic ovarian disease. 216 66

Plasma 5 alpha-androstane-3 alpha, 17 beta diol (Adiol) glucuronide levels were determined using a reliable radioimmunoassay involving hydrolysis with E. coli beta-glucuronidase, diethylether extraction, and Celite column chromatography. Conditions ensuring optimal hydrolysis were determined as well as quality control criteria. Sixty-eight male out-patients wre studied. These subjects were divided into three age groups: I (n = 21; age 20-35 years), II (n = 21; age: 36-50 years), and III (n = 26; age: 51-70 years). Patients under 50 years of age had infertility with no abnormalities upon sperm analysis. Older patients had erectile dysfunction. All subjects had serum gonadotropin (FSH and LH) and prolactin levels within the normal range for age. Adiol glucuronide levels (mean +/- SD) were as follows: 5.0 +/- 2.2 ng/ml (range: 1.6-9.5), 5.4 +/- 3.8 ng/ml (range 1.4-16.0) and 4.5 +/- 2.5 ng/ml (range 1.2-9.3) in groups I, II and III respectively. A trend towards lower Adiol glucuronide levels with advancing age was found but there was no significant difference between group III and the other two groups. Similarly, no significant correlation was found between Adiol glucuronide levels and age (r = -0.12). Conversely, a significant correlation (r = 0.37; p less than 0.01) was observed between Adiol glucuronide levels and bioavailable testosterone (T) levels. This finding might be the consequence of a certain enhancement of 5 alpha-reductase activity with age and/or the non significant decrease with age of another precursor.
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PMID:[Age-related changes in plasma androstanediol glucuronide in men]. 227 25

Pregnant rats were irradiated with 2.1 Gy gamma-ray of 60Co at day 20 of gestation. Seventy days after birth, the body weight of the fetally irradiated male pups was significantly lower than the control. The testes, ventral prostates and seminal vesicles were atrophied by irradiation, whereas no decreased weight of the adrenals was observed. Histological examination of the testes of the irradiated rats revealed a complete disappearance of germinal cells. Sertoli cells and Leydig cells appeared normal, and no apparent histological difference was observed in the adrenals between the control and the irradiated rats. Activities of microsomal delta 5-3 beta-hydroxysteroid dehydrogenase (HSD) + isomerase, 17 alpha-hydroxylase/C17,20-lyase, 17 beta-HSD and 7 alpha-hydroxylase per pair of testes were decreased in the irradiated rats (36-86% of the control). In contrast, no decreased activity of 20 alpha-HSD in the cytosol fraction was observed by irradiation. No decreased activity of adrenocortical enzymes, such as delta 5-3 beta-HSD + isomerase, 21-hydroxylase, 11 beta-/18-hydroxylase and 5 alpha-reductase, was also observed in the irradiated group. Concentrations of LH, FSH, TSH, prolactin, testosterone, progesterone and aldosterone in serum were measured by radioimmunoassay. Only the FSH concentration was significantly increased by the irradiation, while no difference was found in the concentration of other hormones. It was concluded that irreversible damage was induced in spermatogenesis and androgen production by the fetal irradiation, whereas corticoidogenesis was not affected.
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PMID:Steroidogenesis in the testes and the adrenals of adult male rats after gamma-irradiation in utero at late pregnancy. 230 42

The present studies examined the hormonal regulation of 5 alpha-reductase activity in cultured immature rat Leydig cells. Within the testis 5 alpha-reductase was concentrated in the interstitial cell compartment, and among interstitial cells, the enzyme was localized primarily in Band 3 of Percoll density gradients, which contains the majority of Leydig cells. Among various factors reported previously to stimulate testicular 5 alpha-reductase activity when administered in vivo to immature rats (LH/hCG, FSH, luteinizing hormone releasing hormone or prolactin), only LH/hCG directly stimulated 5 alpha-reductase activity of cultured immature Band 3 cells. Neither growth hormone which was reported previously to stimulate hepatic 5 alpha-reductase activity, nor insulin, insulin-like growth factor-I, or epidermal growth factor, which have been reported to modulate Leydig cell function, had any effect on 5 alpha-reductase activity of Band 3 cells. These studies suggest that the major factor directly stimulating 5 alpha-reductase activity in Leydig cells during early maturation is LH. However, it is possible that other factors acting indirectly may modulate the maturational rise in 5 alpha-reductase activity.
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PMID:Regulation of 5 alpha-reductase activity in cultured immature leydig cells by human chorionic gonadotropin. 236 32

Small cell aggregates of functional interstitial tissue were isolated from ovaries of 21- to 24-day-old rats, and their biochemical properties were studied in miniature cultures of 500-4000 cells. The isolated interstitial cells expressed high amounts of the mitochondrial cholesterol side-chain cleavage cytochrome P-450, visualized by immunofluorescent staining. Freshly isolated cells also expressed high activities of 17 alpha-hydroxylase and 17:20-lyase, which were assayed by TLC analysis of [3H]progesterone metabolites. The TLC technique revealed the immediate conversion of progesterone to 5 alpha-reduced progestins. Consequently, no aromatizable androgens were produced but, accumulation of androsterone resulted instead from the direct action of 17 alpha-hydroxylase on 3 alpha-hydroxy-5 alpha-pregnane-20-one (pregnanolone). Both the immunoreactive levels of cholesterol side-chain cleavage cytochrome P-450 and the rate of the 17:20-lyase activity declined rapidly during culture. However, addition of LH to the medium restored both enzymes, indicating the presence of functional LH receptors. The latter were also demonstrable by their ability to evoke cAMP formation in response to LH, but not to FSH. The activity of 5 alpha-reductase in the interstitial cells was much higher (3-fold) than its activity in the granulosa cells. Unlike 17:20 lyase, the activity of 5 alpha-reductase did not decay in culture, nor was it affected by LH. We thus established a novel and sensitive experimental method to isolate and study a minute population of ovarian cells which, unlike the follicular granulosa and theca cells, are enigmatically differentiated at the early stages of ovarian development.
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PMID:Microanalysis of hormone responsive ovarian interstitial gland cells in miniature culture. 253 84

Nine elderly men with prostatic carcinoma underwent treatment with a LHRH-agonist (Zoladex, ICI) for 3-6 months. At the end of the treatment period the patients underwent subcapsular orchidectomy. Testicular tissue was incubated with different tritiated testosterone precursors. Conversion mediated by several testicular steroidogenic enzymes was compared between Zoladex-treated patients and nineteen non-treated patients who underwent orchidectomy because of prostatic carcinoma. Serum concentrations of LH, FSH and testosterone were determined before and during treatment in the treated patients. The LHRH agonist treatment induced significantly decreased conversion mediated by the enzymes 3 beta-hydroxysteroid dehydrogenase, 17 alpha-hydroxylase and C17-20 lyase. Conversion mediated by 17 beta-ketosteroid reductase was also decreased although not as dramatically as the other enzymes, while conversion mediated by 20 alpha-dehydrogenase was increased. Serum concentrations of testosterone decreased to castration levels. Serum gonadotrophins decreased but remained within normal levels suggesting that "desensitization" at the pituitary level was not the only mechanism of action of the LHRH-agonist.
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PMID:Influence of continuous luteinizing hormone-releasing hormone agonist treatment on steroidogenic enzymes in the human testis. 296 9

We investigated whether Sertoli cell spent media (SCM) contain a factor (or factors) which influences steroidogenesis in Leydig cells. Freshly prepared prepubertal interstitial cells or Percoll-purified Leydig cells and similar cells cultured in the presence or absence of LH were incubated for 24 h in the presence of a 5 alpha-reductase inhibitor and in the presence or absence of SCM. The accumulation of C19-steroids (testosterone and androstenedione), C21-steroids (progesterone, 17 alpha-hydroxyprogesterone and 20 alpha-hydroxypregn-4-en-3-one) and cyclic AMP was measured by radioimmunoassay. It could be demonstrated that SCM contains a factor that stimulates an early step in the steroidogenic pathway but at the same time hampers the conversion of C21-precursors into androgens. In freshly prepared Leydig cells the final effect is a stimulation of the androgen output. In Leydig cells cultured in the absence of LH, mainly C21-steroid output is increased. These biological effects resemble those observed with LHRH and its agonists. The activity of the Sertoli cell factor is not affected by an LHRH antagonist, however, and maximally effective concentrations of the factor and LHRH have additive effects, suggesting that they act by distinct receptor systems. Preliminary characterization shows that the factor in SCM is a thermolabile protein with a MW greater than 10 000. The production of the factor decreases during prolonged culture in serum-free medium. Addition of fetal calf serum causes a marked and dose-dependent increase in the production or activity of the factor. Several permanent cell lines (B16, Bowes, BHK, Ratec, RK13, Vero) produce a factor with comparable biological effects on Leydig cells. Nonetheless, the observation that the production of this factor by Sertoli cell cultures is stimulated by FSH and dbcAMP suggests that, in the testis, it may play a role in the paracrine control of Leydig cell function.
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PMID:A factor in spent media from Sertoli-cell-enriched cultures that stimulates steroidogenesis in Leydig cells. 298 67

The effects of FSH and (Bu)2cAMP on synthesis of the components of the cholesterol side-chain cleavage (SCC) enzyme complex, namely SCC cytochrome P-450 (P-450scc), the iron-sulfur protein adrenodoxin (ISP), and NADPH:ISP reductase (Red), were investigated in granulosa cells obtained from ovaries of immature estrogen-primed rats cultured for up to 72 h in defined medium in the presence or absence of FSH and (Bu)2cAMP. The cells were lysed, and proteins were subjected to polyacrylamide gel electrophoresis, followed by immunoblotting using antibodies specific to bovine adrenocortical P-450scc, ISP, and Red. A time-dependent increase was observed in the specific contents of these three components of SCC, but not of the reference mitochondrial protein, F1-ATPase, upon treatment with FSH or (Bu)2cAMP. The increase in the content of these three enzymes was accompanied by a rise in progesterone and 20 alpha-hydroxyprogesterone production. The synthesis of P-450scc, ISP, and Red increased 3- to 4-fold with time upon FSH or (Bu)2cAMP treatment respectively, as evidenced by pulse labeling of the cell proteins with [35S]methionine, followed by immunoprecipitation. Immunoprecipitation of P-450scc and ISP from an in vitro translation system programmed by RNA isolated from cultured cells revealed that treatment with FSH or (Bu)2cAMP resulted in an increase in the levels of translatable mRNA specific for these proteins, and that the initial products of translation were precursor forms of cytochrome P-450scc and ISP, similar to those observed in bovine adrenal and granulosa cells. It is concluded that in cultured rat ovarian granulosa cells, FSH induces the synthesis of cytochrome P-450scc, ISP, and Red by increasing the content of translatable mRNA coding for the precursor forms of these enzymes and that this action is mediated by cAMP. Furthermore, the effects of FSH and (Bu)2cAMP provide an explanation for the action of these compounds to stimulate progestin synthesis in cultured ovarian cells.
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PMID:Synthesis of the cholesterol side-chain cleavage enzymes in cultured rat ovarian granulosa cells: induction by follicle-stimulating hormone and dibutyryl adenosine 3',5'-monophosphate. 301 93

We evaluated testicular function in 15 men with the Martin-Bell (fragile-X) mental retardation syndrome. Macro-orchidism was present in all subjects. Their mean serum LH and FSH levels and plasma testosterone and dihydrotestosterone levels were normal. The mean plasma levels of androstenedione, 17-hydroxyprogesterone, and progesterone were slightly elevated above the normal range, whereas the plasma levels of dehydroepiandrosterone and dehydroepiandrosterone-sulfate were normal. The response in the levels of plasma testosterone following a 5 day period of hCG stimulation was normal in 8 subjects and there was no abnormal accumulation of androgen precursors. The level of 5 alpha-reductase activity and androgen receptor binding was normal in genital skin fibroblasts derived from 3 of these patients. The response of gonadotropin secretion to GnRH stimulation was normal in the 8 men who were tested. Therefore, our data are consistent with the hypothesis that testicular enlargement in men with the Martin-Bell syndrome is not mediated by hormonal factors.
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PMID:Gonadal function in men with the Martin-Bell (fragile-X) syndrome. 308 5


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